It has been demonstrated that human plasma low-density lipoprotein (LDL) isolated from individuals differs structurally among normal and hyperlipoproteinemic subjects. These findings emphasize the need to study the structure of LDL, and this research is primarily concerned with the LDL apoproteins (apo-LDL). Apo-LL is a glycoprotein which, following delipidation, may be solubilized in 70 percent formic acid, and in this solvent its hydrodynamic properties can be studied. Using sedimentation velocity and equilibrium methods, we are investigating the molecular weight of apo-LDL. Apo-LDL also electrophoreses in 70 percent formic acid, and the suggestion of electrophoretic heterogeneity is under study and raises the possibility of apo-LDLs which differ in charge and hence in structure. In 1964 Bernfeld and Kelley reported that native LDL can be subjected to limited tryptic digestion with liberation of about 10 percent of the protein, as small peptides, but without the dissociation of lipid from a stable lipoprotein core. This observation provides the basis of our investigation of the organization of apo-LDL within native LDL. A stable tryptic core may be isolated, and the properties of this lipoprotein core, the characterization of the large hydrophobic peptides of the core, and the study of the small peptides liberated, presumably, from the surface of LDL are under study. Of interest will be a comparison of these structural features in LDL isolated from different subjects to determine whether differences in the structure of native LDL reflect differences in the structure or organization of apo-LDL as it exists within the native lipoprotein. In order to delineate possible structural differences it may be necessary to sequence specific regions of apo-LDL and thus, hopefully, correlate variations in the primary structure of this protein with differences in the molecular weights of native LDL. BIBLIOGRAPHIC REFERENCES: Phair, R.D.; Hammond, M.G.; Bowden, J. A.; Fried, M.; Fisher, W.R.; and Berman, M. "A preliminary model for human lipoprotein metabolism in hyperlipoproteinemia," Fed. Proc. 34:2263-2270, 1975. Fisher, W.R. "The hyperbeta- and hyperprebeta-lipoproteinemias." In Low-Density Lipoproteins, edited by C.E. Day. Plenum Press, NY, 1976. (In press).